Uptake of labeled histidine into rat basophilic leukemia (2H3) cells was time and temperature dependent. This uptake system had high affinity for histidine (Km, 24 +- 4 muM). The histidine was decarboxylated to form histamine and this histamine was incorporated to storage granules. However, some of it was lost to the medium. In elutriated cells histidine uptake and decarboxylation were low in small cells and progressively increased with cell size, but decreased as the cells approached cell division. The changes in kinetic constants suggest a decrease in number of active sites for histidine transport as cells approach cell division. Alpha-fluoromethyl histamine (Alpha-FMH), a suicide inhibitor of histidine decarboxylase, like histidine was taken up by 2H3 cells but had lower affinity (Km, 170MuM) for the uptake system than histidine. Alpha-FMH partially inhibited the uptake and decarboxylation of histamine. In cultured cells (1-4 days) low concentrations of AlphaFMH stimulated histiding decarboxylase activity while high concentrations were inhibitory. Histamine levels changed accordingly. However AlphaFMH had no effect on cell division.